AQP4_RAT
ID AQP4_RAT Reviewed; 323 AA.
AC P47863; A0A0G2K4I1; Q8CIY8;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Aquaporin-4;
DE Short=AQP-4;
DE AltName: Full=Mercurial-insensitive water channel {ECO:0000303|PubMed:7509789};
DE Short=MIWC {ECO:0000303|PubMed:7509789};
DE AltName: Full=WCH4;
GN Name=Aqp4;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND LONG), FUNCTION, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP HIS-201.
RC TISSUE=Brain;
RX PubMed=7528931; DOI=10.1073/pnas.91.26.13052;
RA Jung J.S., Bhat R.V., Preston G.M., Guggino W.B., Baraban J.M., Agre P.;
RT "Molecular characterization of an aquaporin cDNA from brain: candidate
RT osmoreceptor and regulator of water balance.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:13052-13056(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
RC TISSUE=Brain;
RA Chen D., Chen J., Jing K., Simon R.P., Graham S.H.;
RT "Isolation of an aquaporin-4 water channel (AQP4) gene induced following
RT cerebral ischemia from the rat brain using modified subtractive
RT hybridization and differential screening.";
RL Submitted (APR-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND SHORT), FUNCTION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=7509789; DOI=10.1016/s0021-9258(17)37486-0;
RA Hasegawa H., Ma T., Skach W., Matthay M.A., Verkman A.S.;
RT "Molecular cloning of a mercurial-insensitive water channel expressed in
RT selected water-transporting tissues.";
RL J. Biol. Chem. 269:5497-5500(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [5] {ECO:0000312|EMBL:EDL75044.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000312|EMBL:AAN40408.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-69 (ISOFORM 3), AND TISSUE
RP SPECIFICITY.
RX PubMed=12359252; DOI=10.1016/s0006-291x(02)02296-9;
RA Mhatre A.N., Stern R.E., Li J., Lalwani A.K.;
RT "Aquaporin 4 expression in the mammalian inner ear and its role in
RT hearing.";
RL Biochem. Biophys. Res. Commun. 297:987-996(2002).
RN [7]
RP PHOSPHORYLATION AT SER-285.
RX PubMed=12692561; DOI=10.1038/nbt819;
RA Wu C.C., MacCoss M.J., Howell K.E., Yates J.R. III;
RT "A method for the comprehensive proteomic analysis of membrane proteins.";
RL Nat. Biotechnol. 21:532-538(2003).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-321, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [9]
RP SUBCELLULAR LOCATION, SUBUNIT, ALTERNATIVE SPLICING, PALMITOYLATION AT
RP CYS-13 AND CYS-17 (ISOFORM LONG), MUTAGENESIS OF CYS-13 AND CYS-17, AND
RP TISSUE SPECIFICITY.
RX PubMed=18179769; DOI=10.1016/j.bbamem.2007.12.007;
RA Suzuki H., Nishikawa K., Hiroaki Y., Fujiyoshi Y.;
RT "Formation of aquaporin-4 arrays is inhibited by palmitoylation of N-
RT terminal cysteine residues.";
RL Biochim. Biophys. Acta 1778:1181-1189(2008).
RN [10]
RP PHOSPHORYLATION AT SER-180, FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS
RP OF SER-180.
RX PubMed=19800950; DOI=10.1016/j.neuroscience.2009.09.072;
RA Moeller H.B., Fenton R.A., Zeuthen T., Macaulay N.;
RT "Vasopressin-dependent short-term regulation of aquaporin 4 expressed in
RT Xenopus oocytes.";
RL Neuroscience 164:1674-1684(2009).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-276 AND SER-285, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [12]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, SUBUNIT, AND ALTERNATIVE
RP SPLICING.
RX PubMed=29055082; DOI=10.1111/jcmm.13401;
RA Rosito S., Nicchia G.P., Palazzo C., Lia A., Buccoliero C., Pisani F.,
RA Svelto M., Trojano M., Frigeri A.;
RT "Supramolecular aggregation of aquaporin-4 is different in muscle and
RT brain: correlation with tissue susceptibility in neuromyelitis optica.";
RL J. Cell. Mol. Med. 22:1236-1246(2018).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 23-323, FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, TOPOLOGY, DOMAIN, AND TISSUE SPECIFICITY.
RX PubMed=16325200; DOI=10.1016/j.jmb.2005.10.081;
RA Hiroaki Y., Tani K., Kamegawa A., Gyobu N., Nishikawa K., Suzuki H.,
RA Walz T., Sasaki S., Mitsuoka K., Kimura K., Mizoguchi A., Fujiyoshi Y.;
RT "Implications of the aquaporin-4 structure on array formation and cell
RT adhesion.";
RL J. Mol. Biol. 355:628-639(2006).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 23-323, SUBUNIT, TOPOLOGY, AND
RP DOMAIN.
RX PubMed=19406128; DOI=10.1016/j.jmb.2009.04.049;
RA Tani K., Mitsuma T., Hiroaki Y., Kamegawa A., Nishikawa K., Tanimura Y.,
RA Fujiyoshi Y.;
RT "Mechanism of aquaporin-4's fast and highly selective water conduction and
RT proton exclusion.";
RL J. Mol. Biol. 389:694-706(2009).
CC -!- FUNCTION: Forms a water-specific channel (PubMed:7528931,
CC PubMed:7509789, PubMed:19800950). Plays an important role in brain
CC water homeostasis and in glymphatic solute transport. Required for a
CC normal rate of water exchange across the blood brain interface.
CC Required for normal levels of cerebrospinal fluid influx into the brain
CC cortex and parenchyma along paravascular spaces that surround
CC penetrating arteries, and for normal drainage of interstitial fluid
CC along paravenous drainage pathways. Thereby, it is required for normal
CC clearance of solutes from the brain interstitial fluid, including
CC soluble beta-amyloid peptides derived from APP. Plays a redundant role
CC in urinary water homeostasis and urinary concentrating ability (By
CC similarity). {ECO:0000250|UniProtKB:P55088,
CC ECO:0000269|PubMed:19800950, ECO:0000269|PubMed:7509789,
CC ECO:0000269|PubMed:7528931}.
CC -!- SUBUNIT: Homotetramer (PubMed:16325200, PubMed:19406128). The tetramers
CC can form oligomeric arrays in membranes (PubMed:18179769,
CC PubMed:29055082). The size of the oligomers differs between tissues and
CC is smaller in skeletal muscle than in brain (PubMed:29055082).
CC Interaction between AQP4 oligomeric arrays in close-by cells can
CC contribute to cell-cell adhesion (PubMed:16325200). Part of a complex
CC containing MLC1, TRPV4, HEPACAM and ATP1B1 (By similarity).
CC {ECO:0000250|UniProtKB:P55087, ECO:0000269|PubMed:16325200,
CC ECO:0000269|PubMed:18179769, ECO:0000269|PubMed:19406128,
CC ECO:0000269|PubMed:29055082}.
CC -!- INTERACTION:
CC P47863; Q9ERZ8: Trpv4; NbExp=4; IntAct=EBI-15907593, EBI-10095418;
CC P47863; Q9HBA0: TRPV4; Xeno; NbExp=2; IntAct=EBI-15907593, EBI-962786;
CC P47863-1; Q9ERZ8: Trpv4; NbExp=2; IntAct=EBI-15907676, EBI-10095418;
CC P47863-1; Q9HBA0: TRPV4; Xeno; NbExp=2; IntAct=EBI-15907676, EBI-962786;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:16325200,
CC ECO:0000269|PubMed:18179769, ECO:0000269|PubMed:19800950,
CC ECO:0000269|PubMed:29055082, ECO:0000269|PubMed:7509789,
CC ECO:0000269|PubMed:7528931}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16325200, ECO:0000269|PubMed:19406128}. Basolateral
CC cell membrane {ECO:0000250|UniProtKB:P55088}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:16325200, ECO:0000269|PubMed:19406128}.
CC Endosome membrane {ECO:0000305|PubMed:19800950}. Cell membrane,
CC sarcolemma {ECO:0000269|PubMed:29055082}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16325200, ECO:0000269|PubMed:19406128}. Cell
CC projection {ECO:0000269|PubMed:29055082}. Note=Activation of the
CC vasopressin receptor AVPR1A triggers AQP4 phosphorylation at Ser-180
CC and promotes its internalization from the cell membrane
CC (PubMed:19800950). Detected on brain astrocyte processes and astrocyte
CC endfeet close to capillaries (PubMed:29055082).
CC {ECO:0000269|PubMed:19800950, ECO:0000269|PubMed:29055082}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long; Synonyms=AQP4-M1 {ECO:0000303|PubMed:29055082};
CC IsoId=P47863-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P47863-2; Sequence=VSP_003235;
CC Name=3; Synonyms=AQP4-M23 {ECO:0000303|PubMed:29055082};
CC IsoId=P47863-3; Sequence=VSP_060149;
CC -!- TISSUE SPECIFICITY: Detected in cerebellum (PubMed:18179769,
CC PubMed:29055082). Detected on pericapillary astrocyte endfeet in
CC cerebellum, and in skeletal muscle (PubMed:29055082). Detected in glial
CC lamellae in the hypothalamus (at protein level) (PubMed:16325200).
CC Abundant in mature brain cortex, cerebellum and spinal cord. Highly
CC expressed in the ependymal cell lining the aqueductal system and over
CC the space of the brain in contact with the subarachnoid space. Detected
CC in paraventricular and supraoptic nuclei, the granule cell layer of the
CC dentate gyrus and the Purkinje cell layer in the cerebellum. Only
CC weakly detectable in eye, kidney, intestine, and lung (PubMed:7528931).
CC {ECO:0000269|PubMed:16325200, ECO:0000269|PubMed:18179769,
CC ECO:0000269|PubMed:29055082, ECO:0000269|PubMed:7528931}.
CC -!- DEVELOPMENTAL STAGE: Detected in mature brain, but not in fetal brain.
CC {ECO:0000269|PubMed:7528931}.
CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing three
CC membrane-spanning domains and a pore-forming loop with the signature
CC motif Asn-Pro-Ala (NPA). {ECO:0000269|PubMed:16325200,
CC ECO:0000269|PubMed:19406128}.
CC -!- PTM: Phosphorylation by PKC at Ser-180 promotes internalization from
CC the cell membrane, reducing the conductance by 50% (PubMed:19800950).
CC Phosphorylation by PKG at Ser-111 in response to glutamate increases
CC conductance by 40% (By similarity). {ECO:0000250|UniProtKB:P55088,
CC ECO:0000269|PubMed:19800950}.
CC -!- PTM: Isoform Long: Palmitoylated on its N-terminal region. Isoform 3:
CC Not palmitoylated. {ECO:0000269|PubMed:18179769}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; U14007; AAC52152.1; -; mRNA.
DR EMBL; AF144082; AAD37965.1; -; mRNA.
DR EMBL; L27588; AAA17730.1; -; mRNA.
DR EMBL; AABR07031271; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH474065; EDL75044.1; -; Genomic_DNA.
DR EMBL; AF541968; AAN40408.1; -; Genomic_DNA.
DR PIR; I59283; I59283.
DR RefSeq; NP_001135838.1; NM_001142366.2. [P47863-3]
DR RefSeq; NP_001257487.1; NM_001270558.2. [P47863-2]
DR RefSeq; NP_036957.1; NM_012825.4. [P47863-1]
DR RefSeq; XP_017456346.1; XM_017600857.1. [P47863-3]
DR PDB; 2D57; X-ray; 3.20 A; A=23-323.
DR PDB; 2ZZ9; X-ray; 2.80 A; A=23-323.
DR PDB; 3IYZ; EM; 10.00 A; A=23-323.
DR PDBsum; 2D57; -.
DR PDBsum; 2ZZ9; -.
DR PDBsum; 3IYZ; -.
DR AlphaFoldDB; P47863; -.
DR SMR; P47863; -.
DR BioGRID; 247332; 5.
DR CORUM; P47863; -.
DR DIP; DIP-59601N; -.
DR IntAct; P47863; 2.
DR STRING; 10116.ENSRNOP00000063720; -.
DR GlyGen; P47863; 1 site.
DR iPTMnet; P47863; -.
DR PhosphoSitePlus; P47863; -.
DR SwissPalm; P47863; -.
DR PaxDb; P47863; -.
DR PRIDE; P47863; -.
DR GeneID; 25293; -.
DR KEGG; rno:25293; -.
DR CTD; 361; -.
DR RGD; 2143; Aqp4.
DR VEuPathDB; HostDB:ENSRNOG00000016043; -.
DR eggNOG; KOG0223; Eukaryota.
DR InParanoid; P47863; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P47863; -.
DR Reactome; R-RNO-432040; Vasopressin regulates renal water homeostasis via Aquaporins.
DR Reactome; R-RNO-432047; Passive transport by Aquaporins.
DR EvolutionaryTrace; P47863; -.
DR PRO; PR:P47863; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Proteomes; UP000234681; Chromosome 18.
DR Bgee; ENSRNOG00000016043; Expressed in cerebellum and 14 other tissues.
DR ExpressionAtlas; P47863; baseline and differential.
DR Genevisible; P47863; RN.
DR GO; GO:0097450; C:astrocyte end-foot; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IDA:RGD.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:RGD.
DR GO; GO:0031253; C:cell projection membrane; IDA:RGD.
DR GO; GO:0005911; C:cell-cell junction; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; IEA:GOC.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0042383; C:sarcolemma; IDA:UniProtKB.
DR GO; GO:0030315; C:T-tubule; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR GO; GO:0015670; P:carbon dioxide transport; IDA:UniProtKB.
DR GO; GO:0098609; P:cell-cell adhesion; IMP:UniProtKB.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEP:RGD.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IMP:RGD.
DR GO; GO:0071346; P:cellular response to interferon-gamma; ISO:RGD.
DR GO; GO:0071347; P:cellular response to interleukin-1; IEP:RGD.
DR GO; GO:0071354; P:cellular response to interleukin-6; IEP:RGD.
DR GO; GO:0009992; P:cellular water homeostasis; IDA:UniProtKB.
DR GO; GO:0090660; P:cerebrospinal fluid circulation; ISS:UniProtKB.
DR GO; GO:0033326; P:cerebrospinal fluid secretion; ISO:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0042538; P:hyperosmotic salinity response; IEP:RGD.
DR GO; GO:0050891; P:multicellular organismal water homeostasis; ISO:RGD.
DR GO; GO:0060354; P:negative regulation of cell adhesion molecule production; IMP:RGD.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:RGD.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:RGD.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0010574; P:regulation of vascular endothelial growth factor production; IMP:RGD.
DR GO; GO:0070295; P:renal water absorption; ISO:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0009314; P:response to radiation; IEP:RGD.
DR GO; GO:0007605; P:sensory perception of sound; ISO:RGD.
DR GO; GO:0030104; P:water homeostasis; ISS:UniProtKB.
DR GO; GO:0006833; P:water transport; IDA:RGD.
DR CDD; cd00333; MIP; 1.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR034294; Aquaporin_transptr.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Cell projection;
KW Endosome; Glycoprotein; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..323
FT /note="Aquaporin-4"
FT /id="PRO_0000063950"
FT TOPO_DOM 1..36
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 37..57
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 58..69
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 70..89
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 90..93
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT INTRAMEM 94..101
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 102..115
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 116..136
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 137..155
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 156..176
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 177..184
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 185..205
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 206..208
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT INTRAMEM 209..222
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 223..231
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TRANSMEM 232..252
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT TOPO_DOM 253..323
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:16325200,
FT ECO:0000269|PubMed:19406128"
FT MOTIF 97..99
FT /note="NPA 1"
FT /evidence="ECO:0000305|PubMed:16325200,
FT ECO:0000305|PubMed:19406128"
FT MOTIF 213..215
FT /note="NPA 2"
FT /evidence="ECO:0000305|PubMed:16325200,
FT ECO:0000305|PubMed:19406128"
FT MOD_RES 111
FT /note="Phosphoserine; by PKG"
FT /evidence="ECO:0000250|UniProtKB:P55088"
FT MOD_RES 180
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000269|PubMed:19800950"
FT MOD_RES 276
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 285
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:12692561,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 289
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P55088"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT LIPID 13
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18179769"
FT LIPID 17
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:18179769"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..22
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_060149"
FT VAR_SEQ 150..204
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000305"
FT /id="VSP_003235"
FT MUTAGEN 13
FT /note="C->A: Reduced palmitoylation. Loss of
FT palmitoylation; when associated with A-17."
FT /evidence="ECO:0000269|PubMed:18179769"
FT MUTAGEN 17
FT /note="C->A: Reduced palmitoylation. Loss of
FT palmitoylation; when associated with A-13."
FT /evidence="ECO:0000269|PubMed:18179769"
FT MUTAGEN 180
FT /note="S->A: Decreases internalization from the cell
FT membrane in response to PKC activation."
FT /evidence="ECO:0000269|PubMed:19800950"
FT MUTAGEN 201
FT /note="H->P: Partial loss of transport activity."
FT /evidence="ECO:0000269|PubMed:7528931"
FT CONFLICT 69
FT /note="D -> A (in Ref. 6; AAN40408)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="H -> P (in Ref. 3; AAA17730)"
FT /evidence="ECO:0000305"
FT HELIX 32..53
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT STRAND 60..63
FT /evidence="ECO:0007829|PDB:2D57"
FT HELIX 70..88
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 98..106
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT TURN 112..115
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 116..134
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT TURN 138..140
FT /evidence="ECO:0007829|PDB:2D57"
FT HELIX 141..143
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 156..177
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 189..208
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 214..224
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT TURN 228..231
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT HELIX 232..249
FT /evidence="ECO:0007829|PDB:2ZZ9"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:2ZZ9"
SQ SEQUENCE 323 AA; 34480 MW; 6ADD24647713609D CRC64;
MSDGAAARRW GKCGPPCSRE SIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSVGSTINWG
GSENPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIT
AQCLGAIIGA GILYLVTPPS VVGGLGVTTV HGNLTAGHGL LVELIITFQL VFTIFASCDS
KRTDVTGSVA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG
AVLAGALYEY VFCPDVELKR RLKEAFSKAA QQTKGSYMEV EDNRSQVETE DLILKPGVVH
VIDIDRGDEK KGKDSSGEVL SSV
